Loss of XIST Impairs Human Mammary Stem Cell Differentiation and Increases Tumorigenicity Through Enhancer and Mediator Complex Hyperactivation

2021 ◽  
Author(s):  
Laia Richart ◽  
Mary-Loup Picod ◽  
Michel Wassef ◽  
Manon Macario ◽  
Setareh Aflaki ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Differentiation ◽  
Stem Cell Differentiation ◽  
Mammary Stem Cell ◽  
Mediator Complex ◽  
Mammary Stem

scholarly journals Perturbation-Expression Analysis Identifies RUNX1 as a Regulator of Human Mammary Stem Cell Differentiation

2015 ◽  
Vol 11 (4) ◽  
pp. e1004161 ◽  
Author(s):  
Ethan S. Sokol ◽  
Sandhya Sanduja ◽  
Dexter X. Jin ◽  
Daniel H. Miller ◽  
Robert A. Mathis ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Differentiation ◽  
Expression Analysis ◽  
Stem Cell Differentiation ◽  
Mammary Stem Cell ◽  
Mammary Stem

scholarly journals Impact of estrogen population pharmacokinetics on a QSP model of mammary stem cell differentiation into myoepithelial cells

2021 ◽  
Vol 6 (10) ◽  
pp. 10861-10880
Author(s):  
Justin Le Sauteur-Robitaille ◽  
◽  
Zhe Si Yu ◽  
Morgan Craig ◽  
Keyword(s):  
Stem Cell ◽  
Cell Differentiation ◽  
Population Pharmacokinetics ◽  
Myoepithelial Cell ◽  
Ethinyl Estradiol ◽  
Stem Cell Differentiation ◽  
Myoepithelial Cells ◽  
Cell Production ◽  
Mammary Stem ◽  
Critical Components

<abstract> <p>Stem cell differentiation cascades are critical components of healthy tissue maintenance. Dysregulation in these systems can lead to serious diseases, including cancer. Myoepithelial mammary cells are produced from differentiated mammary stem cells in processes regulated, in part, by estrogen signalling and concentrations. To quantify and predict the production of mammary myoepithelial cell production by estrogen, we developed a mechanistic, quantitative systems pharmacology (QSP) model that includes the explicit characterization of free and unbound estrogen concentrations in circulation. Linking this model to a previously developed population pharmacokinetics model for ethinyl estradiol, a synthetic form of estrogen included in oral contraceptives, we predicted the effects of estrogen on myoepithelial cell development. Interestingly, pharmacokinetic intraindividual variability alone did not significantly impact on our modelos predictions, suggesting that combinations of physiological and pharmacokinetic variability drive heterogeneity in mechanistic QSP models. Our model is one component of an improved understanding of mammary myoepithelial cell production and development, and our results support the call for mechanistically constructed systems models for disease and pharmaceutical modelling.</p> </abstract>

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